title: Pioglitazone improves obesity type diabetic nephropathy: relation to the mitigation of renal oxidative reaction.
abstract: Medications to treat hyperglycemia and hyperinsulinemia are expected to inhibit the accumulation of advanced glycation end-products in the diabetic kidney and improve renal function by inhibiting oxidative reactions. In this study, we examined the effect of pioglitazone, an insulin sensitizer, on diabetic nephropathy. Feed containing pioglitazone at 0.01 or 0.02% was given to Zucker-fatty rats for 27 weeks. Pioglitazone reduced plasma glucose, plasma insulin, and blood HbAlc levels. It also decreased plasma total cholesterol, triglyceride, phospholipid and cystatin C levels and inhibited the increase in urine of 8-hydroxydeoxyguanosine and in plasma of malondialdehyde. In the histopathological examinations, pioglitazone inhibited diffusive or nodular thickening of the mesangial matrix, atrophy of the proximal convoluted tubule, thickening of the basement membrane of the tubule, and mild cellular infiltration (mostly small lymphocytes) in the stroma. Furthermore, pioglitazone inhibited the mRNA expression of the receptor for advanced glycation end-products (RAGE) and that of transforming growth factor-beta. Long-term administration of pioglitazone improved hyperglycemia lipid profiles, hypercholesterolemia, and hyperinsulinemia and had a protective effect on diabetic nephropathy in Zucker-fatty rats.
authors.affiliation: Department of Pharmacobiology and Therapeutics, Faculty of Pharmacy, Meijo University, Gifu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirasawa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Matsui
authors.forename: Kazusuke
authors.initials: K
authors.lastname: Yamane
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Yabuki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Toyoshi
authors.forename: Kohei
authors.initials: K
authors.lastname: Kyuki
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nagamatsu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008315:Malondialdehyde / Q000652:urine; D009765:Obesity / Q000150:complications*; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000097:blood; D000077205:Pioglitazone; D051381:Rats; D011924:Rats, Zucker; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001786:Blood Glucose; D002784:Cholesterol; D055316:Cystatin C; D015891:Cystatins; D006442:Glycated Hemoglobin; D006147:Guanine; D007004:Hypoglycemic Agents; D007328:Insulin; D008315:Malondialdehyde; D010743:Phospholipids; D000077205:Pioglitazone; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D014280:Triglycerides; C525032:Cst3 protein, rat; C517652:hemoglobin A1c protein, human; C078307:8-oxo-7,8-dihydrodeoxyguanine